Translating the Neurobiology of Addiction Into New Treatments: Medication Assisted Recovery

Barbara J. Mason, Ph.D.Pearson Family Professor, Committee on the Neurobiology of Addictive Disorders

Co-Director, The Pearson Center for Alcoholism and Addiction Research

SAB Malibu BeachSept. 29 & 30, 2013

Source: SAMHSA National Survey on Drug Use and Health, 2010

Numbers in Thousands

Medication Targets in the Cycle of Alcoholism and Addiction

Protracted Withdrawal

Binge/Intoxication

AcuteWithdrawal

Opioid Dependence naltrexone (ReVia, Vivitrol): $41M ** methadone (Dolophine): $44M buprenorphine (Suboxone) $1.2BNicotine Dependence varenicline (Chantix): ~$710M nicotine patch, nicotine gum: OTC $3.4B bupropion (Zyban): ~$550M **Alcohol Dependence naltrexone (ReVia, Vivitrol): $41M ** acamprosate (Campral): $81M

* From: http:www.evaluatepharma.com** Includes all indications

Nucleus Accumbens (Binge-intoxication) — Structure in the front bottom of the brain involved in the rewarding effects of drugs of abuse that is a key part of the binge/intoxication stage of addiction. Contains reward neurotransmitters dopamine and opioid peptides that are involved in the euphoric effects of addiction.

Extended Amygdala (Withdrawal-negative affect) — A set of structures in the front middle of the brain that include the central nucleus of the amygdala, bed nucleus of the stria terminalis, and part of the nucleus accumbens. Contains brain “stress” neurotransmitter corticotropin-releasing factor that produces dysphoria during withdrawal in addiction.

Prefrontal Cortex (“Craving”)— Structure in the front top of the brain involved in executive function that plays a key role in relapse to addiction. Executive function combines elements of delay in gratification and inhibition to allow healthful choices and decisions. Contains the major excitatory neurotransmitter glutamate that reawakens “craving”.

Existing medications• disulfiram• naltrexone• methadone• varenicline• buprenorphine

Future targets• partial agonists (intoxication blockers)• drug vaccines (intoxication blockers)

Existing medications• methadone• nicotine patch• buprenorphine• varenicline

Future targets• GABA modulators (homeostatic resetters)• CRF1 antagonists (stress reducers)• opioid antagonists (dysphoria reducer)

Existing medications• acamprosate• buproprion

Future targets• GABA modulators (homeostatic resetters)• CRF1 antagonists (stress reducers)• Glutamate modulators (habit reducers)

Substance abuse treatment has proven efficacy, is cost effective, and has gained parity with other medical disorders for reimbursement by 3rd party payorsIdentify and pre-clinically validate novel targetsRe-purpose available drugs and shelved investigational drugs for other indicationsDevelop vaccines and novel routes of administration•Use human laboratory studies for proof of concept •Increase addiction medicine training programs and fellowships to expand the network of prescribers